InterPro domain: IPR038354

Vitamin K epoxide reductase (VKOR) recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a co-factor that is essential for the posttranslational gamma-carboxylation of several blood coagulation factors [ 1 ]. VKORC1, the catalytic subunit of the VKOR complex, is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea [ 2 , 3 ]. Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner [ 4 , 5 ]. In fact, in some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases [ 6 ]. VKOR is part of a disulphide bond formation pathway that uses electrons from cysteines of newly synthesized proteins to reduce a quinone [ 6 ].

1. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427, 537-41
2. Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Trends Biochem. Sci. 29, 289-92
3. Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer. Nat Commun 5, 3110
4. Identification of an atypical membrane protein involved in the formation of protein disulfide bonds in oxygenic photosynthetic organisms. J. Biol. Chem. 283, 15762-70
5. Bacterial species exhibit diversity in their mechanisms and capacity for protein disulfide bond formation. Proc. Natl. Acad. Sci. U.S.A. 105, 11933-8
6. Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463, 507-12